This invention relates to prognostics for breast cancer based on the gene expression profiles of biological samples.
In breast cancers, prognosis is determined primarily by the presence or absence of metastases in draining axillary lymph nodes. However, in approximately one third of women with breast cancer who have negative lymph nodes, the disease recurs and about one third of patients with positive lymph nodes are free of disease ten years after local or regional therapy. Furthermore, an increasing proportion of breast cancers are being diagnosed at an early stage because of increased awareness and wider use of screening modalities. Universal application of systematic therapy to these patients often leads to over-treatment. According to the St Gallen and NIH consensus, 70-80% of the Stage I and II patients would not have developed distant metastases without adjuvant treatment and may potentially suffer from the side effects. These data highlight the need for more sensitive and specific prognostic assays that could significantly reduce the number of patients that receive unnecessary treatment.
Tumor size and lymphatic or vascular invasion have been found to be of significant prognostic value in several studies. Quantitative pathological features, i.e. nuclear morphology, DNA content and proliferative activity may further demarcate tumors that have a high chance of micrometastases. Known molecular genetic changes that affect patient outcome include Her2/NEU over-expression, DNA amplifications, p53 mutations, ER/PR status, uPA and PAI expression. Because the metastatic cascade is a complex process that includes multiple steps, single factors that contribute to tumor process have limitations for prognostic assessment. The gene expression profiles of this invention will provide increased prognostic power.